San Diego, California – Rakuten Medical Inc. announced the commencement of a Phase 1, open-label, dose-escalation, clinical trial (RM-1995-102; jRCT number: 2031220721) in Japan for Alluminox™ treatment (photoimmunotherapy), utilizing our newly developed anti-CD25 antibody-dye conjugate, RM-1995 and a device for laser illumination at a wavelength of 690 nm. The trial focuses on patients with advanced or recurrent solid tumors with liver metastasis.
This is a Phase 1 clinical trial for patients with advanced or recurrent solid tumors with at least one metastatic liver lesion that can be illuminated with a laser and for whom no standard treatment is available. The study will evaluate the safety and tolerability of the treatment with the drug as a monotherapy (Phase 1a and 1b) and in combination with pembrolizumab (Phase 1c) to determine the maximum tolerated dose (MTD) or maximum accepted dose (MAD) and the recommended dose to be used in a Phase 2 clinical trial. The safety of the medical device for liver metastases will also be evaluated.
Primary sites of liver metastasis include tumors of the digestive system, such as colorectal, stomach, and pancreatic cancers, as well as breast and lung cancers. The liver is a frequent metastatic organ in various cancers1, and these metastatic lesions are associated with a poor prognosis2.
Hiroshi Mikitani, Co-CEO of Rakuten Medical, said: “We are delighted to have commenced the clinical trial of Alluminox™ treatment using our second newly developed compound, RM-1995, in Japan. Liver metastasis is a common occurrence in various cancers, and with the limited efficacy of current treatments. We hold firm in our belief that this treatment has the potential to be a beacon of hope for patients awaiting novel therapies. It has been ten years since my father's pancreatic cancer became the catalyst for my involvement in developing Rakuten Medical’s Alluminox technology. I sense we have taken a significant step towards the development of a treatment for a wide range of cancers, including pancreatic cancer.
In November 2021, the development of this study, "Development of innovative cancer therapy targeting regulatory T cells using anti-CD25 antibody-dye complex (RM-1995)," was selected by the Japan Agency for Medical Research and Development (AMED). This study is conducted with the support of AMED.
About Rakuten Medical, Inc.
Rakuten Medical, Inc. is a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox™ platform, which, in pre-clinical studies, has been shown to induce rapid and selective cell killing and tumor necrosis. Alluminox therapies have not yet been approved outside of Japan. Rakuten Medical is committed to its mission to conquer cancer by delivering our innovative treatments as quickly as possible to as many patients as possible all over the world. The company has offices in 6 countries, including the United States, where it is headquartered, Japan, the Netherlands, Taiwan, Switzerland and India. For more information, visit www.rakuten-med.com.
RM-1995, developed by Rakuten Medical using its Alluminox™ platform, is an antibody-dye conjugate comprised of a monoclonal antibody specific for cell-surface interleukin 2 (IL-2) receptor α-chain (CD25) and IRDye® 700DX (IR700), a light-activatable dye. RM-1995 photoimmunotherapy is designed to specifically kill CD25+ regulatory T cells (Tregs) within solid tumors once illuminated with 690nm, intended to deliver nonthermal red light3. Rakuten Medical’s preclinical data has suggested that RM-1995 photoimmunotherapy treatment can be utilized to specifically deplete intratumoral Tregs, thereby alleviating local Treg-mediated restraint within the tumor microenvironment, rapidly improving the CD8 T cell: Treg ratio, and reinvigorating effector CD8+ T cell responses.
About Alluminox™ platform
The Alluminox™ platform is an investigational technology platform based on a cancer therapy called photoimmunotherapy, which was developed by Dr. Hisataka Kobayashi and team from the National Cancer Institute in the United States. Rakuten Medical is developing the Alluminox platform as a technology consisting of a drug, device, and other related components. The drug component of the platform consists of a targeting moiety conjugated with one or more dyes leading to selective cell surface binding. The device component consists of a light source that locally illuminates the targeted cells with light to transiently activate the drug. Pre-clinical data have shown that this activation elicits rapid and selective necrosis of targeted cells through a biophysical process that compromises the membrane integrity of the targeted cells. Therapies developed on the Alluminox platform may also result in local and systemic innate and adaptive immune activation due to immunogenic cell death of the targeted cancer cells and/or the removal of targeted immunosuppressive cells within the tumor microenvironment. Outside of Japan, Alluminox therapies have not yet been approved by any regulatory authority.
Forward Looking Statements
This press release contains forward looking statements that correspond to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements include various risks, uncertainties, and assumptions that may cause Rakuten Medical’s business plans and results to differ from the anticipated results and expectations expressed in these statements. These “forward looking statements” contain information about the status and development of our products, including RM-1995, the Alluminox™ platform and IRDye® 700DX, as well as other regulatory and marketing authorization efforts, the potential benefits, efficacy, and safety of RM-1995 and other therapies created using the Alluminox™ platform, and the status of regulatory filings. The approval and commercial success of such therapies may not be achieved, and the results and effects shown in pre-clinical studies and data may not be replicated in clinical trials. Such statements may include words such as “expect,” “believe,” “hope,” “estimate,” “looks as though,” “anticipate,” “intend,” “may,” “might,” “suggest,” “plan,” “strategy,” “will,” “hopeful,” “excited,” “do,” “aims,” “develop” and similar expressions. Forward-looking statements are neither historical facts nor assurances of future performance. Such forward-looking statements are based upon Rakuten Medical’s current beliefs, expectations, and assumptions regarding the future of its business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of Rakuten Medical’s control. Rakuten Medical’s actual results and financial condition may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. In addition, this press release uses terms such as “expected,” “important,” “notable,” and “novel” to express opinions about clinical trial data. Ongoing clinical trial studies include various risks and uncertainties, in particular, problems that arise during the manufacturing stage of RM-1995 or other product candidates, the occurrence of adverse safety events, situations in failure to demonstrate therapeutic benefits, and other various risks and uncertainties, both reasonable and unreasonable. For this reason, actual results, including regulatory approvals and uncertainties in the commercialization process of RM-1995 or other product candidates, may differ from published information. Except to the extent required by applicable law, we undertake no obligation to publicly update this or any other forward-looking statement, whether because of new information, future developments or events, changes in assumptions, changes in the factors affecting forward-looking statements. If one or more forward-looking statement(s) is updated, no inference should be drawn that additional updates will be made to those or other forward-looking statements.
1. Danielle T. Metastatic Liver Cancer; MSD Manual Professional Edition (Accessed on July 26, 2023)
2. Yamamoto M. Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021. J Hepatobiliary Pancreat Sci., 28, 1-25.
3. Sato, K. et al. Spatially selective depletion of tumor-associated regulatory T cells with near-infrared photoimmunotherapy. Sci Transl Med 8, 352ra110, doi:10.1126/scitranslmed.aaf6843 (2016).